The objective of the third year of this project is to study in further detail the mechanisms responsible for the formation of urinary pCO in highly alkaline urine. The studies performed in previous years have utilized carbonic anhydrase administration to underscore the mechanisms responsible for a high urinary pCO2. We now plan to assess the effect of carbonic anhydrase inhibitors on distal acidification. Another aspect of this proposal to be further investigated is the distal acidification defect induced by glucose and insulin administration as shown by preliminary studies in our laboratory. This study is aimed at characterizing this acidification defect and the mechanisms responsible for its generation.